He Lan-Xiang, Zhang Gui-Mei, Feng Zuo-Hua
Department of Biochemisitry and Molecular Biology, Tongji Medical College, Huazhong University of Sciences and Technology, Wuhan 430030, China.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2005 Jan;21(1):100-2, 117.
To explore the antitumor effects of dendritic cells (DCs) modified with different forms of hepatocellular cancer antigens.
DCs were modified with freeze-thawed H22 cell lysate, small molecular H22 peptides and Hsp70-H22 peptide complex, respectively. The cytotoxicity of DCs-activated CTLs to H22 cells was detected by MTT colorimetry. The expression level of IFN-gamma mRNA in splenocytes was detected by RT-PCR. The DCs modified with different antigens were used to immunize mice and then the suppressive effects on the growth of tumor were measured.
The DCs modified with H22 peptides alone could not activate CTLs. The ability to activate CTLs by DCs modified with Hsp70-H22 peptide complex was stronger than that by DCs modified with freeze-thawed H22 lysate, with the killing rates of CTLs being 47.3% and 18.3%, respectively. The expression level of IFN-gamma mRNA in 3 groups of splenocytes was consistent with the killing rate of CTLs.The growth of H22 cells in mice immunized with DCs modified with freeze-thawed H22 lysate or Hsp70-H22 peptide complex was suppressed, but the suppressive effect of the latter was stronger than that of the former. The tumorigenesis rate in the Hsp70-22 peptide complex group was only 40%, whereas the tumorigenesis rates in the other two groups were 100%.
Hsp70-H22 peptide complex is a strong sensitizer for DCs, which participates in immune rejection of tumor through activating CTLs and inducing CD4 (+) T cells to differentiate into Th1 cells.
探讨经不同形式的肝癌抗原修饰的树突状细胞（DCs）的抗肿瘤作用。
分别用冻融的H22细胞裂解物、小分子H22肽和热休克蛋白70-H22肽复合物修饰DCs。采用MTT比色法检测DCs激活的细胞毒性T淋巴细胞（CTLs）对H22细胞的杀伤活性。采用逆转录聚合酶链反应（RT-PCR）检测脾细胞中γ干扰素（IFN-γ）mRNA的表达水平。用经不同抗原修饰的DCs免疫小鼠，然后检测其对肿瘤生长的抑制作用。
单独用H22肽修饰的DCs不能激活CTLs。热休克蛋白70-H22肽复合物修饰的DCs激活CTLs的能力强于冻融的H22裂解物修饰的DCs，CTLs的杀伤率分别为47.3%和18.3%。3组脾细胞中IFN-γ mRNA的表达水平与CTLs的杀伤率一致。用冻融的H22裂解物或热休克蛋白70-H22肽复合物修饰的DCs免疫的小鼠体内H22细胞的生长受到抑制，但后者的抑制作用强于前者。热休克蛋白70-22肽复合物组的肿瘤发生率仅为40%，而其他两组的肿瘤发生率均为100%。
热休克蛋白70-H22肽复合物是DCs的强致敏剂，其通过激活CTLs和诱导CD4（+）T细胞分化为Th1细胞参与肿瘤的免疫排斥反应。
